Mitochondrial transcription termination factor 3 (MTERF3)

Mitochondrial transcription termination factor 3 (MTERF3) is a nuclear-encoded protein localized to mitochondria, where it plays a critical role in regulating mitochondrial gene expression. It acts as a conserved negative regulator of mitochondrial DNA (mtDNA) transcription by binding to the promoter region and repressing transcription initiation. Beyond this primary function, MTERF3 is essential for the assembly of the large mitochondrial ribosomal subunit (39S), thereby coordinating transcription and translation within mitochondria[1][2][3]. Its activity has profound effects on mitochondrial function, ATP production, and cellular metabolism. In cancer, notably hepatocellular carcinoma, MTERF3 is overexpressed and associated with poor prognosis, cell proliferation, and resistance to apoptosis. Targeting MTERF3 disrupts mitochondrial homeostasis, increases reactive oxygen species (ROS), and activates apoptotic signaling pathways (such as p38 MAPK), leading to cell cycle arrest and cell death[1]. MTERF3 does not currently have clinically approved drugs targeting it, and manipulation of its function must consider broad impacts on cellular energy metabolism and homeostasis in both malignant and non-malignant cells[1][3][2][5].

Other names

Transcription termination factor 3, mitochondrialMTERFD1CGI-12FLJ10939mTERF domain-containing protein 1, mitochondrialMTERF domain containing 1MTERF domain-containing protein 1, mitochondrial

Restoring negative regulation of mtDNA transcription (e.g., MTERF3 agonists could reduce excess transcription, possibly relevant in mitochondrial diseases); Inhibition of cell proliferation via induction of mitochondrial dysfunction and ROS accumulation (e.g., in cancer therapy targeting MTERF3); Modulation of ribosome biogenesis pathways